Background: Hypothalamic neuropeptides, orexins, play pivotal roles in nociception and pain modulation. Objective: In this study, we investigated the effect of the administration of orexin into the paraventricular nucleus (PVT) on the development of morphine-induced analgesia in rats. Method. Male Wistar rats weighing 250-300 g received subcutaneous (s.c.) chronic morphine (6, 16, 26, 36, 46, 56 and 66 mg/kg, 2 ml/kg) at an interval of 24 hours for 7 days. Animals were divided into two experimental groups in which the orexin (100 μM, 200 nl) and its vehicle were microinjected into the PVT nucleus for 7 days before each morphine injection. Then, the formalin test was performed for the assessment of pain-related behaviors. Results: The results demonstrated that the rats pretreated by intra-PVT orexin exhibited higher pain-related behaviors than the morphine-treated group. The analgesic effects of morphine were significantly lower in orexin plus morphine-treated rats than the vehicle plus morphine-treated ones. Conclusion: Our findings suggested that the animals receiving the prolonged intra-PVT application of orexin before morphine injection demonstrated a significant increase in the development of nociceptive behaviors in all phases. Therefore, the present study highlighted a new area of the brain involved in the effect of orexin on analgesia induced by morphine.

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